Is XPC p.Arg293Gln (c.878G>A) pathogenic?

XPC p.Arg293Gln (c.878G>A) is classified Likely benign in XPC (ClinVar, Single submitter, 2 submitters; last evaluated 2022-07-01). AlphaMissense: likely benign (0.0889); Ultra-rare (popmax 0.024%, afr).

How common is XPC p.Arg293Gln (c.878G>A) in the general population?

XPC p.Arg293Gln (c.878G>A) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about XPC p.Arg293Gln (c.878G>A)?

AlphaMissense predicts likely benign (score 0.0889) — an in-silico prediction, not a clinical call.

XPC p.Arg293Gln

c.878G>A · rs529962425 · VCV2653581

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0889 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0889	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -9.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.1	GERP 0.52
Regional constraint	o/e 0.97	unconstrained · MANE · 33 kb · p 0.33 · regional, not allelic
Overall
CADD	17.54	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.024% African / African-American · 18/75,038 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.0057% 92/1,613,534 alleles · ultra-rare exomes 77/1,461,222 · genomes 15/152,312 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,169
Remaining individualsnot grpmax-eligible	0.0096%	10,412
European (non-Finnish)	0.00517%	19,340
Admixed American	0.005%	19,991
South Asian	0.0044%	22,739

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: XPC
Protein: p.Arg293Gln
Coding: c.878G>A
MANE Select: NM_004628
dbSNP: rs529962425
Type: single nucleotide variant
Location: chr3:14164835 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.67 · 18 PDB

Full XPC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

XPC p.Arg293Ter Pathogenic ★★ same residue
XPC p.Arg293= Likely benign ★ same residue
XPC c.104-2A>G Likely pathogenic ★★ same type
XPC c.1872+1G>A Likely pathogenic ★★ same type
XPC c.1872+1G>C Pathogenic/Likely pathogenic ★★ same type
XPC c.2033+1G>A Pathogenic/Likely pathogenic ★★ same type
XPC c.2251-1G>C Pathogenic ★★ same type
XPC c.2420+2T>C Pathogenic/Likely pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/xpc-p-arg293gln (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown